Understanding how sensory representations are transformed in the brain is a fundamental problem in neuroscience. An important step in solving this problem is understanding the synaptic interactions within the neural circuit that carries out these transformations. Despite many studies of synaptic transmission in vitro, it remains unclear specifically which aspects of synaptic computation are critical in transforming natural sensory information encoded in spike trains in vivo. This project addresses this question in the Drosophila antennal lobe, where it is possible to characterize the physiology of synapses made between identified neurons whose responses to natural stimuli are well documented in vivo. The Drosophila antennal lobe, an analogue of the vertebrate olfactory bulb, consists of morphologically discrete modules called glomeruli, where axons of olfactory receptor neurons (ORNs) make synaptic contacts with the dendrites of projection neurons (PNs). Local interneurons (LNs) interconnect multiple glomeruli. Prior investigations have already characterized odor-evoked responses from both ORNs and PNs in vivo, and as a result the sensory transformations that occur in this brain region are beginning to be understood. This project examines the synaptic mechanisms underlying these sensory transformations. ORN-PN synaptic transmission will be characterized by recording from identified PNs while electrically stimulating the olfactory nerve. Interglomerular interactions among PNs and LNs will be characterized using genetically encoded "triggers" to selectively stimulate specific neurons in the brain while recording from other genetically-labeled neurons. Specific Aim #1 tests the hypothesis that the specific properties of ORN-PN synapses partially explain several key features of olfactory transformation in the antennal lobe. Specific Aim #2 tests the hypothesis that some characteristics of ORN-PN synaptic transmission are heterogeneous across glomeruli. Specific Aim #3 tests the hypothesis that PNs and LNs interact with each other across glomeruli. This study should substantially contribute to understanding sensory processing in the brain. Specifically, it should help us understand the role of specific synaptic properties in sensory computations. This in turn should inform the study of defects in synaptic transmission (synaptopathies) that affect specific sensory regions in the brain, and may ultimately be useful in the search for molecular interventions to remedy these defects. In addition, research into insect olfaction should help us understand and prevent the spread of insect-borne diseases.